microbio exam 4

protozoa

single cell eukaryotic organisms

severity of illness directly related to infectious dose and number of exposures

amoeba, apicomplexa, cilliates, flagellates

cyst

inactive, nonmotile infective stage of protozoa

excyst

cyst become trophozoite

encyst

trophozoite becomes cyst

trophozoite

motile vegetative stage of protozoa. colonizes/invades host tissues

entamoeba histolytica parasite burden

1-10% world population

3rd leading cause of parasitic death

entamoeba histolytica reservoir

humans

most people are asymptomatic carriers

carriers pass infective cysts

fecal oral, direct contact, sexual activity

entamoeba histolytica pathogenesis

consumed cysts enter GI tract and excyst into trophozoites

T move along intestinal wall, eating RBC, bacteria, protozoa, human cells

T invade colonic mucosa → erosions, ulcers

T encyst → cysts → leave in stool

invasive colonic trophozoites enter bloodstream

if they invade other organs, OFTEN FATAL

entamoeba histolytica clinical presentation

ameobiasis:

• abdominal pain, dysentery, flask shaped ulcers

  • can lead to peritonitis, appendicitis, necrotozing colitis and toxic megacolon

amebic liver abscess

ameobas that resist complement killing can enter hepatic portal vein and colonize liver

Sxs: flank pain, fever, alanine aminotransferase and aspartate in blood tests (marker of liver damage), redddish brown pus “anchovy paste”

can rupture

ameobiasis diagnosis and treatment

stool of “ova and parasites”, look for ameoba with internal RBC

fecal E. histolytica antigen in stool/blood

colonoscopy with examination of aspirates

imaging of liver

treated with Abx

Giardia duodenalis general information

most common parastic GI pathogen in US

human adapted species, major source of infection

other animals can spread it like beavers

fecal oral

low infectious dose

noninvasive

Giardiasis clinical presentation

“beaver fever”

diarrhea, gas, foul smelling greasy flaoting stool, bloating and cramps, dehydration, anorexia and weight loss

Giardia duodenalis PIS

increased risk of IBS

Giardia duodenalis diagnosis

“ova and parasites” unreliable

fecal antigen detection using immunoassays more reliable

Balantidium coli general characteristics

only ciliate known to be able to infect humans

often associated with domesticated pigs (primary reservoir host)

excystment in the SMI → trophozoites invade the intestinal epithelium → trophozoites encyst and are shed in feces

Balantidium coli clinical presentation

usually asymptomatic, presentations may be acute or chronic with abdominal symptoms

can cause severe diarrhoea, weight loss, abdominal pain, dysentery

can be fatal in immunocompromised

does not produce liver, lung, and brain abscesses

Balantidium coli diagnosis

trophozoites in stool

3 intestinal coccidia organisms and their appearance

Cryptosporidium hominis (tiny)

cyclospora cayetanensis (midsize)

Cystoisospora belli (large and ovoid)

intestinal coccidia distinguishing stain

acid fast

intestinal coccidia life cycle

complex, multi stage life cycles

transmitted fecal oral

most common cause of waterborne illness in US

which intestinal coccidia is resistant to chlorine

cryptosporidium

cryptosporidium transmission and environment

excreted as infective oocysts, direct person to person

found in temperate and tropical zones

cyclospora and cystoisospora transmission and environment

oocysts not immediately infectious, 2-6 weeks to become active

person to person unlikely

primarily tropical diseases

intestinal coccidia clinical presentation

voluminous water diarrhea

self limiting disease

can cause chronic disease and biliary tract disease in immunocompromised hosts

intestinal coccidia diagnosis

ova and parasites

acid fast stain of stool

five plasmodium spp. associated with human disease

*P. falciparum (most virulent human malarial parasite)

P. vivax

P. ovale

P. malariae

P. knowlesi

Plasmodium spp. clinical presentation

malaria

uncomplicated disease is an acute febrile illness developing 10-15 days post exposure

• headache, low fever, chills, sweats, nausea, vomiting, malaise, resp distress

• stereotypical dramatic fever and chills not seen in many patients

• prostration, jaundice (liver failure), abnormal behavior, coma seizures → cerebral malaria

• 20% fatality in adults even with therapy

plasmodium falciparum

severity due to infection of RBC in all ages

shortest incubation period

rapid erythrocytic cycle

cause basophilic stippling on infected RBC

knobs on RBC leads to agglutination and cerebral malaria

malaria reservoir and definitive host

reservoir: humans

host: anopheles mosquito

malaria sporogenic cycle

1. mosquito ingests infected blood, male and female gametocytes fuse in the midgut to form zygote

2. zygote transitions to an oocyst and implants in midgut wall

3. oocyst subdivides by meiosis into 8000 sporozoites (haploid)

   1. sporozoites migrate to the salivary gland to transmit to new host

malaria pro-erythrocytes cycle (liver stage)

1. sporozoites injected into human via bite

2. sporozoites rapidly invade liver cells forming hepatic schizonts

3. sporozoites replicate asexually to high levels

   1. schizont rupture releasing merozoites which invade RBC

malaria erythrocyte cycle (blood stage)

1. all forms of malaria infect RBC, multiply to high numbers, rupture the RBS, and release more merozoites into bloodstream

2. released merozoites infect healthy RBC

   1. some become haploid gametocytes

diagnosis of malaria

microscopy is gold standard

thick and thin blood smears stained with giemsa stain

looks for presence of parasites and species level identification

• rings, gametocyctes, basophilic stipling

ring form trophozoites

visualized in thin blood smear of P. falciparum

may posses one or two chromatin dots

control of malaria

insecticide treated bed nets, indoor residual spraying, vector control

Babesia spp. general characteristics

intracellular parasites look like plasmodium spp.

B. microti cause most human infections

deer, cattle, rodent reservoirs

vector: Blacklegged or deer tick

Babesiosis

risk factors: lack of spleen, immunocompromised, old age

many ind are asymptomatic, high fever, shaking chills, malaise, headache, fatigue, hemolytic anemia (dark urine)

maltese crosses in blood smear

leishmaniasis general characteristics

protozoan infectio involving several spp of leishmania

transmitted by sandfly

intracellular pathogens of macrophages

multiple reservoirs

leishmaniases cutaneous disease

90% cases self healing

start as a small papule at bite site

often enlarge and ulcerate with eschar

usually painless

leaves hypopigmented depressed scar

volcano sign

visceral leishmaniasis

aka kala-azar

second largest parasitic killer worldwide after malaria

caused by leishmania donovani

95% infected ind, are asymptomatic

primarily a disease of children, chronically ill, malnourished, IC

pentad of symptoms: fever, cachexia (wasting), hepatosplenomegaly, pancytopenia (low RBC,WBC,platelets), elevated antibodies

mycobacteriaceae

one genus of medical importance: mycobacterium

small, obligate aerobic bacilli, facultative intracellular bacteria

all slow growing

contain unique cell wall: thick PG layer and outer membrane (no LPS)

weakly gram positive, acid fast stain required

mycobacterial cell envelope

thick and complex

considered gram positive due to lack of classical outer membrane

however, the cell is covered by a waxy layer formed by two major lipids that prevents phagocytosis and excludes most Abx

defined by presence of mycolic acids and phenolic glycolipids

tuberculosis epidemiology

reservoir: humans

1/3- ½ latently infected

major cause of death due to infectious disease

transmission: inhalation of aerosols

miliary TB clinical disease

millet granulomas: small focal collections of macrophages known as primary granulomas

characteristic presentation in infants

resulted from failure to control infection and dissemination in blood stream

TB pathogenesis

immune system suppresses active infection within a mature granuloma

→ latent infection

primary active TB clinical disease

5% patients

immune system fails to contain

usually occurs in peripheral portions of lung tissue, highly infectious

spontaneous healing of TB

ranke complex

calcified hilar lymph node and calcified peripheral lung lesion

reactivated (cavitary) TB

active infection die to reemergence of latent bacteria

bacteria liquify calcified granuloma and establish new, active infection of healthy lung tissue

may disseminate to other organs (miliary)

immunocompromised patients

extrapulmonary TB

ACTIVE INFECTION IN ORGANS OTHER THAN LUNGS

immunocompromised patients

Tuberculin skin test

detects exposure

5 units of purified protein derivative (PPD) injected under surface

localized swelling after 48 hr

do not distinguish latent/active

quantiFERON TB gold test

blood samples mixed with synthetic peptides representing two M. tb proteins.

memory T cells release IFN-gamma in response to Tb antigens

HIV patients may not respond

rapid, less invasive, less false positives

do not distinguish latent/active

acid fast staining: ziehl neelsen method

1. sample on slide

2. air dry and heat fix

3. Carbol fuschin stain (PINK)

4. heat and dry

5. decolorize with alcohol

6. counterstain methylene blue (BLUE)

auramine-rhodamine stain

used for TB, less specific but cheaper

flourescent stain → mycobacteria appear bright orange yellow

TB treatment

combination therapy to prevent Abx resistance

8 wk then 18 wk course

DOTS directly observed treatment, short course

M. leprae clinical presentations

leprosy

affects cooler portions of body: skin, upper respiratory passages, anterior segments of eyes, peripheral nerves, testes

disfigurement, deformity, blindness

endemic in US

M. leprae general characteristics

acid fast, cell wall rich in mycolic acids and glycolipids

obligate intracellular pathogen (cant be grown in lab)

reservoir in humans

transmitted via aerosol, long term close contact

incubation 1-30 yr

some humans are genetically resistant

maybe armadillos

M. leprae pathogenesis

replicates within macrophage/dendritic cells, and schwann cells

leads to nerve damage

2 distinct forms of leprosy

paucibacillary (PB) leprosy, tuberculoid

multibacillary (MB) leprosy, lepromatous

leprosy clinical disease

cardinal signs that suggest leprosy: skin lesions (flat, pale or reddish spots, acid fast bacilli smear), enlarged tender peripheral nerves, sensory deficits, loss of hair, hypohydrosis

nerve damage is permanent

mycobacterium ulcerans

slow growing, environmental pathogen

3rd most common cause of mycobacterial disease in humans, accidental host

unlclar transmission

mycobacterium ulcerans clinical disease

buruli ulcer

rarely fatal

pinky purple ulcer

mycobacterium ulcerans virulence factors

mycolactone: cell cycle arrest, apoptosis, necrosis

detected in tissues at base of lesions

fungal pathogens general characteristics

eukaryotes, true nucleus intracellular organelles

yeasts (budding single cells) or molds (filamentous form)

Cryptococcus neoformans general characteristics

budding yeast

transmitted via inhalation of infectious agent

not person to person

Cryptococcus neoformans clinical disease

inhaled spores lead to asymptomatic respiratory infection or pneumonia or tissue necrosis (cavitation)

severe disease can lead to meningoencephalitis

noncalcified nodules on CXR

common cause of disease in those with reduced cell mediated immuntiy like lymphoma, chronic corticosteroid use, transplants, AIDS

hallmark infection of AIDS (80% of cases)

20-30% in healthy hosts

Cryptococcus neoformans lab diagnosis

lumbar puncture needed

only virulent strains grow at 37 C

expression of capsule essential for virulence

capsule on India Ink stain, H&E stain, and white capsule colonies on Sabouraud agar

candida albicans general characteristics

dimorphic fungus commensal in GI/GU tracts

grown at less than 30 C as a yeast (colonization of mucosal surfaces)

grown at 37 C forms hyphae (active tissue invasion)

small, thin walled, ovoid cells

reproduces as budding

gram positive. much larger than most

candida albicans clinical disease

mucocutaneous infections

ex. oral candidiasis, diaper rash

candida albicans treatment

most respond to topical antifungals and keeping skin dry

Histoplasma capsulatum general characteristics

dimorphic fungus that switches from mycelium to yeast and is necessary for virulence (OPPOSITE of C. albicans)

promoted by bat droppings and bat guano. macroconidia (spores) aerosolized by excavation and construction

Histoplasma capsulatum clinical disease

primary infection is pneumonia, nearly all subclinical and unrecognized

forms calcified nodules that look like miliary TB

causes cavitary lesions

Histoplasma capsulatum lab diagnosis

clinical symptoms, CXR, likely negative TB test

slow growth on sabouraud agar

intracellular yeast normally visible within tissue biopsy samples using H&E staining

classification of chlamydias

chlamydial inclusion bodies look like cloaks around the nucleus

obligate intracellular pathogens that cannot replicate outside another living cell. cannot synthesize amino acids or ATP

gram negative, but lack the cage of PG

transmitted by contact or aerosols in some species

alternate between elementary bodies and reticulate bodies

bacterium, not a virus

few recognized species (3 to know)

chlamydia trachomatis general characteristics

pbligate intracellular bacterium

transmitted through direct contact, sexual activity, or intrapartum

different serotypes associated with different clinical presentations

chlamydia trachomatis clinical disease: trachoma

trachoma: disease of the eye caused

disease of poverty, most often in childhood

via personal contact and flies

1. repeate dinfection leads to chronis keratoconjunctivitis and active trachoma

2. scarring of eyelid

3. onward rotation of eyelashes leading to trichiases

4. scratching leads to corneal opacity, vision impairment, blindness

chlamydia trachomatis CD: inclusion conjunctivits

STI commonly seen in young adults and infants

associated with serotypes D-K

hand to eye of genital fluids

symptoms often appear in one eye first

foreign body sensation, pink eye, mucous, crusty lashes, stuck lids, photophobia, decreased vision

usually heals spontaneously

chalmydia trachomatis CD: non-gonococcal urethritis

inflammation of urethra, not cause by gonnorrhea commonly resulting from c. trach serotypes D-K

most common STI in us

often asymptomatic

presents as uncomplicated urethritis, can lead to sterility and PID

chlamydia trachomatis CD: lymphogranuloma venereum

serotypes L1, L2, L3

more virulent and invasive serotypes

STI more common in men

rare in US

enters through breaks in mucosal surfaces and travels via lymphatic vessels to multiply within macrophages and monocytes in regional lymph nodes

starts as small, painless genital or anal ulcer that may go unnoticed or heal itself

weeks later, may develop tender inguinal or femoral lymphadenopathy unilateral

30% boboes rupture

untreated causes chronis progressive inflammation, scaring, fistulas

chronic fistulas can lead to scarring (strictures) frozen pelvis syndrome, and rarely, genital lymphedema

chlamydia psittaci general characteristics

avian disease, birds → mammals

transmitted by inhalation, contact, ingestion

chlamydia psittaci clinical disease

atypical pneumonia, psittacosis

rare respiratory infection in humans

mild symptoms 5-14 days after exposure sometimes turns into pneumonia

Abx are effective, cough may linger

chlamydia pneumoniae clinical disease

upper and lower respiratory tract infections

upper: ear and sinus infections, sore throats

lower: atypical pneumonia, bronchitis, laryngitis

generally mild but complications can develop

diagnosis of chlamydial infection

does not grow on conventional bacteriologic media

isolation in mammalian cell culture is more reliable

c. trachomatis inclusions can be stained with iodine

serological detection using fluorescent Abs

nucleic acid amplification tests now preferred method

complement fixation assay

watcha. video

treatment of chlamydial infections

antibiotics that inhibit protein synthesis are most effective (azithromycin, tetracyclines)

penicillin paradox: sensitive to beta lactams but no PG cell wall

classification of mycoplasma and ureaplasm

smallest and simplest self replicating bacteria

characteristically lack PG and other cell wall components

pleomorphic (spherical, filamentous, bud like branches)

some have terminal tip structure

single plasma membrane

colonies look like fried eggs (not M. pneumoniae)

mycoplasma pneumoniae pathogenesis

extracellular pathogen that targets respiratory epithelium

adheres to epithelial cells via specialized tip structure

causes ciliostasis

mycoplasma pneumoniae clinical disease

atypical pneumonia (walking pneumonia)

clearance of respiratory tract is impeded by ciliostasis → infection of LR

infection and irritation leads to persistent nonproductive cough and mild URI

estimated 15-20% pneumonias

mycoplasma pneumoniae diagnosis

grows slowly on rich medium containing serum

C. pneumoniae does not grow on media.

cold agglutination test

serological and NAATs are available

ureaplasma urealyticum general characteristics

closely related to mycoplasma spp. and produces enzyme urease

breakdown of urea in urogenital tract leads to inflammation

considered an STI

very common

in women if untreated the NGU can lead to inflammation of chorion and amnion

postpartum fever and PID

rickettsiales general characteristics

small, nonmotile, non spore forming bacteria

may be coccus, bacillus, filaments

stain poorly with gram stain

need giemsa of gimenez stain (deep red)

obligate intracellular pathogen

transmitted by various arthopods

rickettsiales life cycles

rickettsia rickettsii replicates within the cytoplasm and spreads to adjacent cells through actin based motility

ehrlichia chaffeensis replicates within dedicated pathogen containing vacuoles (morulae)

rocky mountain spotted fever

bacterial disease spread by infected tick bite

american dog tick and rocky mountain wood tick

cases rising and peak in summer

initial sxs: fever, headache, myalgia, vomiting (5-10 days PI)

later sxs: rash, joint pain, abdominal pain, diarrhea (2-4 days post fever)

small, non itchy dot rash or red pinpoint rash starting at extremities

mortality 5-10%

rickettsia pathogenesis

replication in endothelial cells triggers vasculitis

fluid leaks from bloodstream into surrounding tissues

rocky mountain spotted fever diagnosis

clinical suspicion start treatment imemdiately

culture not useful

gold standard: indirect fluorescent antibody assay

• detects human IgG against bacteria

• requires 2 tests 2 weeks apart

immunostaining of tissue biopsies

rocky mountain spotted fever treatment

tetracyclines

prevention insect repellents, covering, tick checks

Ehrlichia chafeensis clinical disease

ehrlichiosis

may be asymptomatic

initial sxs: (first 5 days) fever, headache, muscle pain, malaise, nausea, vomitting, diarrhea, occasionally rash forms

severe illness if delayed abx, young, old, or IC: meningoencephalitis, respiratpory failure, uncontrolled bleeding, organ failure

fatal in less than 1%

lone star tick

monocytic infection

ehrlichiosis life cycle

elementary bodies taken up into cells

replicate in vacuole and morulae formed

eventually rupture the infected cell releasing infectious EBs

ehrlichiosis diagnosis

blood tests: leukopenia, thrombocytopenia, elevated liver enzymes

blood smear may show morulae

PCR for bacterial DNA

indirect fluorescent antibody test

treatment with tetracyclines

bartonella henselae general characteristics

gram negative rod, poorly stains needs warthin starry stain

highly fastidious to grow

facultative intracellular bacterium: RBC, endothelial cells